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Long COVIDNCT05965739

RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms

A study testing BrainHQ/Active Comparator Activity, BrainHQ and PASC CoRE in people with Long COVID and Long Covid19, run by Duke University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This platform protocol is designed to be flexible so that it is suitable for a wide range of settings within health care systems, for remote settings, and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Long COVID, Long Covid19, Long Covid-19
What is being tested?
BrainHQ/Active Comparator Activity, BrainHQ and PASC CoRE
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
328 participants
Where
1 siteUnited States
Study dates
1 Sep 2023to 17 Dec 2024
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. See NCT05965752 for RECOVER-NEURO: Platform Protocol level inclusion criteria which applies to this appendix

Who cannot join

  • 1. See NCT05965752 for RECOVER-NEURO: Platform Protocol level exclusion criteria which applies to this appendix
  • Additional Appendix (Sub-study) Level Exclusion Criteria:
  • Presence of metal objects in the head or neck
  • Skin disorders or skin-sensitive areas near tDCS stimulation locations that would interfere with electrode placement or increase the risk of stimulation-induced damage, at the investigator's discretion

Trial locations and contacts

1 site in 1 country.

United States1 site

  • All sites listed under NCT05965752

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: RECOVER-NEURO: A Platform Protocol for Evaluation of Interventions for Cognitive Dysfunction in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

This platform protocol is designed to be flexible so that it is suitable for a wide range of settings within health care systems, for remote settings, and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans.

This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating potential interventions for PASC-mediated cognitive dysfunction. The hypothesis is that PASC-associated dysfunction in cognitive domains, such as executive function and attention, may be improved by interventions that selectively focus on enhancing those domains.

This design seeks to evaluate each intervention relative to the Active Comparator. The BrainHQ (alone) arm is important because the intervention is commercially available, accessible, relatively inexpensive, and does not require trained personnel to administer. BrainHQ has been also been proven effective in other studies of cognitive dysfunction such as studies in aging, mild cognitive impairment, traumatic brain injury, among others. The BrainHQ + PASC CoRE arm and the BrainHQ + tDCS arms are suspected to provide cognitive improvements beyond BrainHQ alone through different mechanisms. Both PASC CoRE and tDCS have extensive prior use and have demonstrated utility in improving aspects of cognitive function in other clinical settings..

Read the detailed description

Participants will be randomized to one of the intervention appendices that are actively enrolling at the time of randomization. Intervention appendices may be added or removed according to adaptive design and/or emerging evidence. Various interventions will be studied.

Participants will be randomized equally across the five arms:

  1. Active Comparator (video games)
  2. BrainHQ
  3. BrainHQ + PASC CoRE
  4. BrainHQ + tDCS-active
  5. BrainHQ + tDCS-sham
Being tested
BrainHQ/Active Comparator Activity, BrainHQ, PASC CoRE, tDCS-active, tDCS-sham
Keywords
PASC, Cognitive
Medical subject headings
Post-Acute COVID-19 Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BrainHQ/Active Comparator ActivityOther

    BrainHQ platform provides a set of cognitive activities, like puzzles and games, that are cognitively stimulating and actively engage participants but do not continuously and adaptively challenge them. These activities are designed to be a face-valid, active comparison approach to cognitive therapy, thus participants are blinded, attention time is matched, and overall user experience is identical to the active arms.

  • BrainHQOther

    BrainHQ is an online cognitive training program, and has been used to improve cognitive function among persons with cognitive impairment based on principles of neuroplasticity.

  • PASC CoREOther

    PASC CoRE is a manualized, adaptable cognitive rehabilitation intervention adapted from Goal Management Training and other evidence based programs that improve attention and executive functions, among other cognitive domains.

  • tDCS-activeDevice

    Transcranial direct current stimulation (tDCS) will use a device specifically for home-based use. This device delivers a weak electrical current of 2.0 mA passed through two electrodes placed on the scalp to target the dorsolateral prefrontal cortex region of the brain. The electrodes are single-use for each session and can be attached to a headset by snapping into place.

    The device has a user-friendly interface and a large-button keypad, making it is easy to use at home.

  • tDCS-shamDevice

    tDCS devices used in the sham arm will be pre-programmed to deliver the same ramp up/down at the beginning/end of the 30-minute period as the active arm, except with no current otherwise delivered during the session.

Study groups in NCT05965739
Study groupRoleWhat they receive
BrainHQ Active ComparatorActive comparator5 sessions/week at 30 min/session
Receives: Other: BrainHQ/Active Comparator Activity
BrainHQExperimental5 sessions/week at 30 min/session
Receives: Other: BrainHQ
BrainHQ + PASC CoREExperimentalBrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 1 hr/session
Receives: Other: BrainHQ; Other: PASC CoRE
Brain HQ + tDCS-activeExperimental2.0 mA stimulation delivered for 30 min during each BrainHQ session
Receives: Other: BrainHQ; Device: tDCS-active
Brain HQ + tDCS-shamPlacebo comparatorInactive stimulation delivered for 30 min during each BrainHQ session
Receives: Other: BrainHQ; Device: tDCS-sham

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Everyday Cognition 2 (ECog2)

    Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure the participant's perceived capacity to perform activities related to cognitive function, which could impact major activities of daily living and independence. Score ranges from 1 to 5, with 5 being worst.

    Measured: Baseline to End of Intervention (EOI) (Day 70)

Secondary outcomes (11)

  1. Change in PROMIS-cognitive Function - Short Form 8a (PROMIS-Cog) Total Score

    The PROMIS-Cog is the PROMIS short form for the cognitive function domain and is a self-report, 8-item questionnaire targeting cognitive function in the past seven days. Scores range from 22.4 to 63.5. Higher scores are better.

    Measured: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  2. Change on Auditory Verbal Learning Test

    Trials #1-#5 report the total number correct across 5 trials. Trials #1-5 generate one total score, the individual scores for each trial are not analyzed. The Score for Trials #1-#5 range from 0-75; higher scores are better.

    Trial #8 reports the total number correct. Scores range from 0-15; higher scores are better.

    Trial #9 reports the total number correct recognition hits minus false positive. Scores range from 0-15; higher scores are better.

    Measured: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  3. Change on Symbol Digit Modalities Test

    The Symbol Digit Modalities Test reports the total number correct on the test. Scores range from 0-110. Higher scores are better.

    Measured: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  4. Change in Verbal Fluency

    The Verbal Fluency Semantic reports the total number correct. Scores range from 0-110. Higher scores are better.

    Measured: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  5. Change in Total Time to Complete the Digit Vigilance Test

    Measured: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  6. Change on NIH Toolbox Flanker Inhibitory Control and Attention Test

    The Flanker Inhibitory Control and Attention Test Computed Score ranges from 0-10. Higher scores are better.

    Measured: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  7. Change in CogState Detection Score

    CogState Detection Score is the mean of log10 transformed reaction times. Lower values are better.

    Measured: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  8. Change in CogState Identification Score

    CogState Identification Score is the mean of log10 transformed reaction times for correct responses. Lower values are better.

    Measured: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  9. Change in CogState One Back Primary Score

    CogState One Back Primary Score is the arcsine transformation of the square root of the proportion of correct responses. The scale ranges from 0 to π/2. Higher scores are better.

    Measured: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  10. Change in Everyday Cognition 2 (ECog2)

    Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure the participant's simple reaction time; respond when X happens and Choice reaction time; respond only if X happens.

    Measured: Baseline, EOS (Day 160)

  11. Total Number of Serious Adverse Events (SAEs) or Unanticipated Adverse Device Effects (UADEs)

    An SAE or serious suspected adverse reaction (SAR) or serious adverse reaction an AE that results in any of the following serious outcomes: Death, life-threatening, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, inpatient hospitalization or prolongation of existing hospitalization, congenital abnormality or birth defect, important medical event that may not result in one of the above outcomes, but may jeopardize the health of the study participant or require medical or surgical intervention to prevent one of the above outcomes from occurring. A UADE is any serious adverse effect, problem, or death caused by or associated with a device if that effect was not previously identified in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

    Measured: Baseline to EOS (Day 160)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2023
  2. Study start1 Sep 2023
  3. Primary completion19 Sep 2024
  4. Study completion17 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
To achieve blinding and an equitable randomization probability, a two-step randomization process will be used. The study will employ a simple (unstratified) randomization scheme. At the first stage, each participant will be assigned with equal probability to one of the intervention appendices for which the participant is eligible, after applying any intervention-specific safety exclusions. At the second stage, each participant will be assigned according to the specific appendix's randomization procedure. Participants will have an equal chance of being randomized into any of the intervention groups.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
328 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05965739
Sponsor's protocol ID
Pro00112477_A
Other IDs
OTA-21-015G, 1OT2HL156812-01
Status last verified
Jul 2026
First submitted
25 Jul 2023
Last updated
11 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: The investigators will share the summary of results on the study website: https://recovercovid.org/

Publications

  • Knopman DS, Koltai D, Laskowitz DT, Becker J, Charvet L, Wisnivesky J, Federman A, Silverstein A, Lokhnygina Y, Pilloni G, Haddad M, Mahncke H, Van Vleet T, Huang R, Cox W, Terry D, Karwowski J, McCray N, Lin JJ, McComsey GA, Singh U, Geng LN, Chu HY, Reece R, Moy J, Arvanitakis Z, Parthasarathy S, Patterson TF, Gupta A, Ostrosky-Zeichner L, Parsonnet J, Kiriakopoulos ET, Fong TG, Mullington J, Jolley S, Shah NS, Morimoto SS, Lee-Iannotti JK, Killgore WDS, Dwyer B, Stringer W, Isache C, Frontera JA, Krishnan JA, O'Steen A, James M, Harper BL, Zimmerman KO; RECOVER-NEURO Clinical Trial Group. Evaluation of Interventions for Cognitive Symptoms in Long COVID: A Randomized Clinical Trial. JAMA Neurol. 2026 Jan 1;83(1):49-59. doi: 10.1001/jamaneurol.2025.4415.

    PubMed 41212544

  • Knopman DS, Laskowitz DT, Koltai DC, Charvet LE, Becker JH, Federman AD, Wisnivesky J, Mahncke H, Van Vleet TM, Bateman L, Kim DY, O'Steen A, James M, Silverstein A, Lokhnygina Y, Rich J, Feger BJ, Zimmerman KO. RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC). Trials. 2024 May 17;25(1):326. doi: 10.1186/s13063-024-08156-z.

    PubMed 38755688

Questions about this trial

What is this clinical trial studying?

A study testing BrainHQ/Active Comparator Activity, BrainHQ and PASC CoRE in people with Long COVID and Long Covid19, run by Duke University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Everyday Cognition 2 (ECog2) (time frame: Baseline to End of Intervention (EOI) (Day 70)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05965739, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026; AzTrials last refreshed its copy on 27 Oct 2026.

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